2. Academic Validation
  3. The role of GPD2 on ferroptosis in sepsis-induced acute lung injury

The role of GPD2 on ferroptosis in sepsis-induced acute lung injury

  • Biochem Biophys Res Commun. 2026 Jan 1:794:153066. doi: 10.1016/j.bbrc.2025.153066.
Ying Han 1,  Chunfang Dai 1,  DanDan Hu 1,  Yu Yao 2,  Wanwan Peng 3,  Yijun Zheng 3,  Qiyi Zeng 4,  Hairui Xie 5,  Jinda Huang 6
Affiliations

Affiliations

  • 1 Department of Children Healthcare, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
  • 2 Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
  • 3 Department of Pediatric Intensive Care Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
  • 4 Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
  • 5 Department of Pediatric Endocrinology and Well Child Care, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. Electronic address: [email protected].
  • 6 Department of Pediatric Intensive Care Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, 510180, China. Electronic address: [email protected].
PMID: 41313944 DOI: 10.1016/j.bbrc.2025.153066
Abstract

Sepsis-induced acute lung injury (ALI) is a serious complication that substantially increases mortality in sepsis. Glycerol-3-phosphate dehydrogenase 2 (GPD2), a mitochondrial enzyme, is involved in oxidative stress, inflammation, and Ferroptosis. However, its specific role in sepsis-induced ALI remains unclear. This study explored the role of GPD2 in sepsis-induced ALI. The study employed a cecal ligation and puncture (CLP) mouse model of sepsis, with GPD2 expression knocked down using adeno-associated virus vectors. Selenomethionine (SeMet), a GPX4 activator, was administered 24 h prior to CLP surgery. Increased GPD2 expression was observed in the lungs of septic mice. GPD2 knockdown mice subjected to CLP had a reduced survival rate and exhibited exacerbated lung injury, characterized by increased vascular permeability, neutrophil infiltration, inflammation, and oxidative stress. Moreover, GPD2 knockdown significantly promoted Ferroptosis in the lungs of septic mice. Notably, SeMet not only inhibited Ferroptosis but also partially reversed the lung injury exacerbated by GPD2 knockdown in septic mice. Our results suggest that GPD2 may protect against pulmonary vascular permeability, neutrophil infiltration, oxidative stress, and inflammatory responses in septic mouse lung tissues by suppressing Ferroptosis through the activation of the GPX4 pathway. These findings suggest that GPD2 could be a potential therapeutic target for sepsis-induced ALI.

Keywords

Ferroptosis; GPD2; GPX4; Sepsis-induced acute lung injury.

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